MSH6 (MutS homolog 6)

NGS analysis of the tumor tissue revealed a pathogenic BRCA2 variant (c.1813delA, p.Ile605TyrTer9), which provides a potential target for personalized therapy. This case report highlights the co-segregation of a rare pathogenic MSH2 variant in a Tunisian family and underscores its clinical implications for improving the management and surveillance of patients with Lynch syndrome.

An exploratory approach consisting of unmasking the results of the NGS analysis of 123 « research » genes involved in the carcinogenesis was applied to the 447 patients tested negative for the different genes of our diagnostic panel. This approach failed to identify other susceptibility genes to pancreatic adenocarcinoma.

Subsequently, endometrioid adenocarcinoma was diagnosed, and in view of the family history, an underlying genetic disorder was suspected and later confirmed as LS with a pathogenic MSH6 variant, representing only the second reported case of MSH6-associated pituitary adenoma. Surgical management included hysterectomy with bilateral salpingo-oophorectomy, aortopelvic lymphadenectomy, and omental biopsy. This case underscores the importance of early diagnosis and lifelong monitoring in CD to reduce mortality from uncontrolled hypercortisolism, while highlighting a possible association between LS and ACTH-secreting pituitary adenomas, particularly those with MSH6 mutations.

P2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=20 --> 0 | Trial completion date: Sep 2032 --> Jan 2026 | Initiation date: Apr 2026 --> Oct 2025 | Not yet recruiting --> Withdrawn | Trial primary completion date: Sep 2030 --> Jan 2026

P=N/A, N=20000, Recruiting, Arbor Research Collaborative for Health | N=10000 --> 20000

This copula-based meta-analysis identifies gene-specific risks of endometrial and ovarian cancer in female Lynch syndrome carriers, supporting personalized gynecologic surveillance. It also notes higher breast cancer risks in MSH6 and PMS2 carriers, but conflicting evidence from large perspective databases prevents definitive conclusions about breast cancer as part of the Lynch syndrome spectrum.

P1/2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=30 --> 0 | Trial completion date: Dec 2032 --> Jan 2026 | Initiation date: Feb 2026 --> Sep 2025 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2030 --> Jan 2026

The supernatant/precipitate of vaginal lavage fluid has significant clinical significance for early screening of endometrial cancer and may also have potential clinical value in guiding targeted therapy and evaluating prognosis. Vaginal lavage fluid gene sequencing may serve as a new method for initial screening of endometrial cancer.

Although dMMR was associated with initial treatment resistance, its unique immunogenicity was found to influence disease progression and subsequent treatment options. These findings suggested that MMR testing in LA-HNSCC patients had significant clinical value, not only aiding in the identification of patients who might benefit from subsequent immunotherapy but also potentially informing initial treatment strategies, such as the prospective exploration of combined immunotherapy approaches.

P2, N=30, Not yet recruiting, Women's Hospital School Of Medicine Zhejiang University

MLH1 loss identifies a subset of MMRd ECs with worse outcomes and lower CD8+ densities supporting substratification of this molecular subtype. Grade, histotype, ER, PR, L1CAM, CTNNB1 and p53 status do not add prognostic refinement within MMRd EC.

Genomic classifier tools help identifying aggressiveness of cancers and aid in personalized treatment decision-making. Joint efforts of multidisciplinary physicians are crucial to improve health outcomes for patients with PCa across the spectrum of this disease.